Journal Club 26.08.06

Chi3l1 Knockout Mitigates Chronic Itch and Cutaneous Inflammation in Mice

Sam Kahler1, Brigid Betz-Stablein1, Fabian Lee1, Joachim Torrano1, Monika Janda2, Clare Primiero1, H, Peter Soyer1 and Dilki Jayasinghe

CHI3L1, also known as YKL-40, is a 40- kDa glycoprotein that is overexpressed
in patients with atopic dermatitis (AD) and is induced by various proinflammatory
cytokines. This protein interacts with multiple receptors (He et al,
2013; Lee et al, 2016), and its serum levels corelate with the severity of AD in
humans. CHI3L1 regulates T helper type 2 cytokines and modulates IgE release
(Curtiss et al, 2023; Lee et al, 2022). Antibody therapy targeting CHI3L1 has
been shown to improve skin inflammation in AD in mice (Lee et al, 2022; Yu
et al, 2024). CHI3L1 also activates IL- 13Ra2 (Kwak et al, 2019). Although IL-
13Ra2 was traditionally considered as a decoy receptor, our studies have
revealed its crucial role in AD associated itch, with increased expression
observed in patients with AD (Xiao et al, 2021). Despite these findings, the
role of CHI3L1 in chronic itch sensation remains largely unexplored. This study
aims to elucidate the role of CHI3L1 in itch by investigating its interactions with
IL-13Ra2 and IL-31 receptor, which are key itch receptors (Meng et al, 2018). In
addition, our study explored the function and the effects of CHI3L1 gene
knockout (KO) on itch generation and related signaling pathways.